The proposed study will develop and employ computational methods to investigate the relationship between the atomic-level architecture and motion of proteins and their biological function. The emphasis will be on protein-protein association phenomena in aqueous media, dealing with both equilibrium and dynamical aspects of association processes. Attention will be directed toward the crucial solvent and electrolyte effects which mediate macromolecular interactions in physiological aqueous solutions. Area One of study will focus on calculating the thermodynamical free energies characterizing the stability of associated proteins in physiological solution conditions. Specifically, equilibrium constants for gelation of normal human hemoglobin (Hb) versus various sickle cell anemia will be elucidated from the findings of this study. Area Two of study will employ the Brownian dynamics simulation method to calculate both protein-protein and protein-ligand diffusional association rates in order to elucidate the specific structural principles of molecular design which relate to the diffusional encounter stage of biochemical reactions. The methodology thus developed will become one of the tools in the arsenal of computer-aided design of chemical agents with biomedical usefulness. Work will be continued on cytochrome redox partners in the electron transport system. Knowledge of the dynamics of the docking step will permit conclusions regarding the the mechanism of electron transfer between heme proteins.